Factor XII Deficiency

Clinical Features of Factor XII Deficiency

Factor XII deficiency was first described in 1955 and initially named Hageman
factor deficiency after the name of the index case (index case is the first
individual identified with a particular phenotype). The original cases were
described as having markedly prolonged clotting times. The frequency of factor
XII deficiency is unknown as individuals carrying mutations in the gene can lack
associated symptoms. At least 10 different mutations have been described in the
factor XII gene. The symptoms of factor XII deficiency do not manifest with
spontaneous or post-surgical bleeding but rather are diagnosed when an
incidental activated partial thromboplastin time (aPTT) is markedly prolonged in
an otherwise asymptomatic patient. The aPTT is a test used to measure the
performance of both the intrinsic and extrinsic
coagulation cascades. A definitive diagnosis of factor XII deficiency is
accomplished by a modified aPTT using factor XII-deficient plasma.

The factor XII gene (symbol F12) is located on chromosome 5q35.3 spanning 12
kb and composed of 16 exons that encode a 615 amino acid preproprotein. Unlike the majority of eukaryotic mRNA genes, the
promoter region of the F12 gene does not contain the typical TATA-box nor the
CAAT-box. This gene structure explains why multiple sites of transcriptional
initiation have been identified in the F12 gene. The factor XII protein contains
multiple domains that are homologous to domains found in tissue type plasminogen
activator (tPA) and fibronectin.